Arteriosclerosis and the resulting myocardial infarction is a leading cause of death, particularly in males. Percutaneous Transluminal Coronary Angioplasty (PTCA) is one treatment used to treat patients with coronary artery disease. PTCA can relieve myocardial ischemia by dilating lumen obstructions, thereby increasing coronary blood flow. Unfortunately, restenosis following PTCA is a significant problem, occurring about 30% of the time within 6 months. Various treatments have been suggested to deal with restenosis.
Administration of compounds for inhibiting vascular smooth muscle cell proliferation and restenosis has been suggested by Cullinan et al. (U.S. Pat. No. 5,462,937). Woods (U.S. Pat. No. 5,180,366) discloses an application of smooth muscle cell anti-proliferation agents, including estrogen, and endothelial growth factor to inhibit restenosis has also been suggested. Growth and division of endothelial cells was said to be promoted while proliferation of smooth muscle cells was believed to be inhibited.
Application of Vascular Endothelial Growth Factor (VEGF) as a post-operative wound healing agent after balloon angioplasty has been suggested, in an amount effective to promote endothelial cell growth by Tischer et al. (U.S. Pat. No. 5,219,739). Inhibition of smooth muscle cell proliferation by administration of an effective amount of Transforming Growth Factor-beta activators or production simulators that act to inhibit vascular smooth muscle cell proliferation has also been proposed by Grainger et al. (U.S. Pat. No. 5,472,985).
It is believed that the more common occurence of restenosis in men compared to women suggests hormones play a role. Oral, transdermal, and implant delivery administration of a therapeutically effective amount of estrogen has been suggested as a method for reducing the risk of heart disease by Hughes et al. (U.S. Pat. No. 5,516,528). A method for reducing restenosis by administering estrogen in a dose sufficient to stimulate synthesis of 27-hydroxychloresterol in the vascular endothelium tissue has also been proposed by Javitt (U.S. Pat. No. 5,376,652). Administration of estrogen to the stenosed, dilated region after PTCA has thus been suggested for the purposes of preventing restenosis.
PTCA is not always a successful solution or even a viable treatment option, as not all stenosed regions can be treated with PTCA. For example, some regions are unreachable with the required size high pressure balloon, which must be advanced through the narrowed, occluded vessel region. Some stenoses are totally blocked, denying entry to a dilitation catheter attempting to advance within. Other vessel regions are too narrow or geometrically too tortuous for dilitation. Damage to weakened vessel walls is a possibility during balloon inflation as well, and may preclude PTCA in some cases. Treatment to increase perfusion to heart tissue, in place of, or in addition to, PTCA would be desirable.